Microfluidic device to investigate factors affecting performance in biosensors designed for transdermal applications

Abstract

In this work we demonstrate a novel microfluidic based platform to investigate the performance of 3D out-of-plane microspike array based glucose and lactate biosensors. The microspike array was bonded with a glass slide and modified with glucose oxidase or lactate oxidase using covalent coupling chemistry. An epoxy-polyurethane based membrane was used to extend the linear working range (from 0 to 25 mM of substrate) of these biosensors. Both lactate and glucose sensors performed well in the clinically relevant substrate concentration range. Glucose microspikes were further investigated with respect to the effects of substrate transfer by incorporation into a microfluidic system. Data from the microfluidic system revealed that the sensor response is mainly dependent on enzyme kinetics rather than membrane permeability to glucose. The robustness of the sensors was demonstrated by its consistency in performance extending over 48 h.

Microfluidic enzymatic biosensing systems: A review

“…Besides their diffusion-limiting behavior, membrane materials should be nontoxic, easy to process and highly permeable to oxygen. Frequently used materials that fulfill these requirements are Nafion (Ges and Baudenbacher, 2010a,b;Li et al, 2013;Rodrigues et al, 2008;Yi et al, 2012), polyurethane (Ahn et al, 2004;Li et al, 2008;Trzebinski et al, 2012) and cellulose (Bindra et al, 1991;Vaidya and Wilkins, 1994). Membranes are typically used with electrodes on which they can be formed by dispensing, spin coating or dipping into an aqueous solution of the membrane material and letting the solvent evaporate.…”

Biosensor Design with Molecular Engineering and Nanotechnology

“…Such structures are long enough to penetrate the top skin layer (the stratum corneum) and access the underlying ISF, but not long enough to reach the nerve endings or capillary bed, hence they are often described as minimally invasive. Various shapes and sizes have been described in the literature, however they can be broadly divided into two categories: microspikes [107,108] and microneedles [109][110][111], the main difference being the latter has the inner channel or lumen that allows extraction of the fluid. As a result, using microneedles allows one to perform the actual diagnostic test in situ whereas in case of microspikes the measurement is non-extractive and practically taken in vivo.…”

“…However, it also introduces the risk of sensor substrate (e.g. biorecognition element or electrode ions) leaking into the surrounding tissue, which can be toxic and induce an immune or inflammatory response [107,113].…”

Editors' Choice—Review—In Vivo and In Vitro Microneedle Based Enzymatic and Non-Enzymatic Continuous Glucose Monitoring Biosensors

“…45 The microneedle arrays were fabricated by following the methods reported by Trzebinski et al 46 The authors reported a closed loop system comprising a CGM sensor and an insulin pump interfaced via suitable control software for management of type 1 diabetes mellitus. The functionalization of working electrodes with glucose dehydrogenase was carried out by following the methods reported by Hanishi et al and Yamashita et al 47,48 The Direct electron transfer (DET) allows the operation of the electrochemical sensor at lower potentials to minimize the effect of interference from acetaminophen, ascorbic acid and uric acid.…”

“…demonstrated a microfluidic based platform to study the performance of 3D out-of-plane micro-spike array-based glucose biosensor. 46 The micro-spike arrays were fabricated by following the method reported by Kim et al 53 The arrays were spin coated with a photoresist material and was glued onto a glass slide patterned with plain silver electrodes. A part of the photoresist material from array platform was dissolved using acetone to expose the metal layer, which was then connected to the silver electrode contact pads using silver epoxy resin ( Figures 5A and 5C).…”